Genes and other biological markers are rapidly being identified that can provide presymptomatic estimates of risk for the eventual development of late-onset diseases. There is widespread public interest in obtaining risk information, particularly as treatments are developed to slow or prevent the onset of degenerative diseases. Many of the recently discovered gene markers are not deterministic genes, but rather susceptibility genes that interact with other, as yet unidentified genes, and with factors such as age, gender, race, family history and environmental exposures. Therefore genotyping individuals for susceptibility genes will require different protocols for providing risk assessment and counseling than those that have been used with deterministic genes. With few restrictions on the marketing and utilization of such tests, their usage may soon increase. Yet, there are almost no data available to understand who (e.g. age, gender, race) would seek susceptibility risk information once it is available; and why they would do so (e.g. to alleviate anxiety, to prepare financially). Nor is there information on the benefits or negative consequences of providing susceptibility risk information that could guide rational clinical decisions or public policy. In its first finding period, the REVEAL Study created original educational and counseling protocols, and enrolled over 150 adult children of patients with Alzheimer's disease (AD) into a randomized clinical trial to examine (1) the characteristics of those persons who sought risk assessment with genetic susceptibility testing, including APOE genotype disclosure and (2) the impact of this disclosure. In the next funding period of the Study (REVEAL II), we will include siblings of patients with AD in the study, and will randomize adult children or siblings to the current Extended Protocol or to a new Condensed Protocol that will more closely minor clinical interactions that could be implemented on a large scale. We will also explore how the impact of genetic susceptibility testing with APOE disclosure varies between younger and older relatives, and between relatives of African American and European American patients with AD. REVEAL II will take place at four clinical centers of care (Boston University, Cornell University, Case Western University and Howard University). Risk assessment using genetic susceptibility testing with APOE genotyping and disclosure, because of its inherent uncertainties, is an ideal model to develop new guidelines for whether and bow best to use susceptibility gene markers in this and other diseases where such markers are, or will be, available in the near future.